Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT03768804 |
| Other study ID # |
13808 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 31, 2019 |
| Est. completion date |
December 2021 |
Study information
| Verified date |
November 2020 |
| Source |
University of Oxford |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In patients with weak pumping function of the heart, uncoordinated contraction of the
chambers can be corrected using a cardiac resynchronization therapy ("CRT") pacemaker. These
devices make patients live longer by improving how the heart pumps and reducing symptoms such
as breathlessness. However, not all patients benefit from CRT and programming devices
optimally can greatly influence success. Predicting the correct timings of contraction
between the atria (top chambers of the heart) and the ventricles (bottom chambers), as well
as between the left and right ventricles, especially when heart rate increases during
exercises, is challenging.
A new approach to optimizing CRT programming has been proposed known as 'fusion-pacing'. This
allows the electrical wave from the heart's own conduction system to merge or fuse with the
impulse from the pacemaker in the left ventricle. The timing of the pacemaker's impulse is
continuously adjusted to measurements the device makes of the hearts natural conduction. What
is not clear is how effective 'fusion-pacing' is during exercise when the hearts natural
conduction changes rapidly and unpredictably. We plan to investigate this by monitoring the
electrocardiogram ("ECG") whilst accurately measuring exercise performance and ability during
a cardiopulmonary exercise test ("CPET") on an exercise bike. We will also ask participants
to rate their perceived exercise intensity to see whether fusion pacing improves ECG
resynchronization, exercise performance, and patients' symptoms compared to standard
programming.
Description:
Heart failure represents a significant health problem, with the last national heart failure
audit demonstrating prevalence in the United Kingdom of 900,000 patients, accounting for 5%
of all acute hospital admissions. This is expected to increase with an ageing population.
Despite improvements in medical therapy, prognosis remains poor, with an in- hospital
mortality of 9.6%, and an estimated mortality of 30-40% at 1 year after diagnosis.
Multiple randomised controlled trials have demonstrated that cardiac resynchronization
therapy pacemaker devices ("CRT") are an effective therapy for patients with poor pumping
function and altered electrical conduction of the heart (left bundle branch block, "LBBB"),
improving both morbidity and mortality. However, only 60-70% of patients notice a symptomatic
improvement with CRT and even in patients who do respond, response can often be improved
further by optimising how the device is programmed.
CRT devices improve coordination of heart pumping by pacing both ventricles of the heart. A
key function of this is to coordinate the timing of contraction of the the atria and the
ventricles (atrio-ventricular, or "AV", optimisation). This allows maximal filling of the
left ventricle with blood. More recently, it has become important not only in standard
bi-ventricular ("BiV") pacing, but to allow left ventricular pacing to be timed with
intrinsic conduction to the right ventricle to provide CRT (so called 'fusion' pacing).
Multiple methods have been described to assess AV optimisation, including echocardiographic
measurements. However, echo based methods are labour intensive, and their value is uncertain.
Device algorithms utilising analysis of the intra-cardiac electrogram ("IEGM") have become an
attractive alternative due to their rapid and automated nature, although evidence suggests
that they may not have clinical benefit over using fixed AV delays. In addition, intrinsic AV
conduction is known to alter with exercise, normally becoming shorter. Optimisation of AV
delays in CRT on exercise has been shown to improve cardiac output. Device algorithms can
therefore allow dynamic adjustment of AV delays as they change with exercise and heart rate
(rate-adaptive AV delay or "RAAVD"). Indeed, use of individually tailored RAAVD in CRT
patients has demonstrated an increase in exercise capacity.
Patients with heart failure and LBBB often have normal intrinsic right ventricular activation
through the right bundle. Utilization of timed left ventricular ("LV") pacing to merge (or
fuse) with this intrinsic conduction may confer benefits over standard BiV pacing, but
requires relatively normal intrinsic AV conduction as well as correct timing of LV pacing to
right ventricular ("RV") activation. Algorithms now exist which allow dynamic reassessment of
intrinsic conduction and so adjustment of the optimal AV delay. They can therefore compensate
for changes in the intrinsic AV delay on exercising, and so maintain adequate fusion pacing
and CRT optimisation. One such software algorithm is SyncAV, developed by Abbott (Abbott
Vascular, 3200 Lakeside Drive, Santa Clara, California 95054-2807). SyncAVTM assesses
intrinsic AV conduction every 256 beats. It then sets a shorter programmed AV delay by
subtracting a set period (known as the "delta" - adjustable but nominally set to 50ms) from
the intrinsic time.
There is some evidence that fusion pacing gives benefit in terms of both acute pumping
function of the heart and long term response to CRT. However, what remains unclear is whether
the effect of dynamic AV optimisation and fusion pacing is maintained on exercise. Firstly,
the re-analysis and adjustment intervals may be insufficient to allow effective fusion
throughout exercise. It is therefore possible that with rapidly changing heart rates this
coordinated timing is lost, leading to inefficient conduction of electricity through the
heart. This could result in large periods of time on exercising without effective CRT and so
poor exercise tolerance. Secondly, there is evidence that in patients with heart failure AV
intervals do not alter with change in heart rate in a similar way to healthy controls. One
study found that the degree of change is greater on exercise, whilst one demonstrated that in
a CRT population only a third of patients had shorter optimal AV delay intervals on exercise,
with a third being unchanged and a third longer. The use of a fixed "delta" in SyncAVTM may
therefore result in incorrect adjustment of AV intervals as intrinsic conduction changes,
with the effectiveness of SyncAV therefore depending on how the intrinsic interval changes.
We will use a prospective single-centre randomized single-blind crossover study to
investigate the effectiveness of SyncAV on exercise, by randomising participants to either
use of SyncAV or fixed AV delays, and then carrying out cardiopulmonary exercise testing
("CPET").
